This laboratory has made progress in two general areas: programmatic and specific radioligands. PROGRAMMATIC. 1) The Biomarkers Consortium approved the proposal of Victor Pike and me to develop further a PET radioligand for inflammation. The Biomarkers Consortium is a collaboration of NIH, FDA, and the pharmaceutical industry and is managed by the Foundation for NIH. The radioligand labels phagocytic inflammatory cells: macrophages in periphery and activated microglia in the brain. We are now planning specific studies to evaluate and disseminate this radioligand for use in multiple PET Centers. 2) Dr. Pike (Director of Radiochemistry) and I post our radioligand information on a public web site to assist the PET community. More specifically, we post the IND (Investigation New Drug) application, including toxicology information and detailed chemical synthesis, the FDA review, and our response to review. 3) Dr. Pike and I continue to direct a joint PhD program in neuroscience with NIH and the Karolinska Institutet (Stockholm, Sweden). We now have about 25 graduate students, about half Swedish and half American. Students have two mentors (one from each institution), spend about half time at each institution. The program has been quite successful, and about 8 students have already received the PhD degree. 5) I wish the NIMH PET program to be a national resource to extramural sites. Towards this goal, I established one useful collaboration with a nearby institution, and I hope to expand to additional universities in the future. Justin McArthur (Johns Hopkins) will recruits and characterizes patients with neurAIDS to NIMH to be scanned with a novel radioligand for inflammation. If the results are successful, the collaborating institution can use the data as preliminary results in a grant application. SPECIFIC RADIOLIGANDS. During the prior year (October 2008 - September 2009), our projects have included: 1) Evaluation of a probe for intracellular signals. Most of the available probes label targets (or receptors) located on the outside of the cell. We are now examining a probe for an intracellular target (phosphodiesterase) that is believed to be involved in the therapeutic actions of antidepressant treatments. We are now studying this radioligand, 11C-rolipram, in depressed patients, before and during treatment with antidepressant medications. 3) Probe for the cannabinoid receptor, which mediates the effects of marijuana. We carefully evaluated this radioligand in healthy subjects and will soon study it in patients with schizophrenia and in marijuana abusers. 4) Probe to measure inflammatory cells. This radioligand has been quite successful, and we have positive preliminary data in multiple sclerosis, stroke, and Alzheimer's disease. 5) Probe to measure a transporter pump at the blood-brain barrier. This efflux transporter, P-gp, blocks the entry of some medications to the brain. Having carefully evaluated the radioligand, 11C-dLop, in healthy subjects, we plan to study the function of this patients with medication-refractory epilepsy and in Alzheimer's disease.